Tenofovir disoproxil is chemically known as 9-[-2-(R)-[[bis[[(isopropoxycarbonyl)oxy]methoxy]phosphinoyl]methoxy]propyl]adenine represented by the following structure:

The above compound is a highly potent antiviral agent, particularly for the therapy or prophylaxis of retroviral infections and belongs to a class of drugs called Nucleoside Reverse Transcriptase Inhibitors (NRTI) which blocks reverse transcriptase an enzyme crucial to viral production in HIV-infected people. These are related to Nucleoside Reverse Transcriptase Inhibitors (NRTI).
U.S. Pat. No. 5,733,788 discloses the process for the preparation of (R)-9-[2-(phosphonomethoxy)propyl]adenine which involves condensation of (R)-9-[2-(hydroxyl)propyl]adenine and Diethyl p-toluenesulfonyloxy methylphosphonate in presence of Lithium hydride in Dimethylformamide followed by dealkylation with Bromotrimethylsilane in Acetonitrile.
U.S. Pat. No. 5,922,695 discloses the synthetic route for the preparation of (R)-9-[2-(phosphonomethoxy)propyl]adenine by condensation of (R)-9-[2-(hydroxyl)propyl]adenine with diethyl p-toluenesulfonyloxymethyl phosphonate in presence of lithium tert-butoxide in tetrahydrofuran followed dealkylation with bromotrimethylsilane in acetonitrile. Further, Tenofovir disoproxil base is obtained as oil which is further converted to fumarate salt.
US 2004/0018150 discloses a process for the preparation of (R)-9-[2-(phosphonomethoxy)propyl]adenine where diethyl p-toluenesulfonyloxymethyl phosphonate is condensed with (R)-9-[2-(hydroxyl)propyl]adenine in presence of Magnesium isopropoxide or Magnesium tert-butoxide in dimethylformamide medium followed by dealkylation with bromotrimethylsilane in acetonitrile with an overall yield 48%.
U.S. Pat. No. 6,465,649 discloses a process for the preparation of (R)-9-[2-(phosphonomethoxy)propyl]adenine by dealkylation of (R)-9-[2-(Diethyl phosphonomethoxy)propyl]adenine with chlorotrimethylsilane in chloroform under pressure.
The above prior art processes describe the processes involves the usage of highly corrosive and expensive reagents like bromotrimethylsilane and chlorotrimethylsilane which require special handling procedures. Such differences provide a compelling basis to develop simple dealkylation procedure for Phosphonate ester with improved yields without using expensive reagents like trialkylsilylhalides.
A number of processes for the preparation of Tenofovir disoproxil have been disclosed. In all the prior art references Tenofovir disoproxil is converted to its fumarate salt without isolating the pure Tenofovir disoproxil base.
The process mentioned above have the disadvantage that it is difficult to separate the intermediates formed during the process, from the end product and, accordingly, extensive purification procedures are required in order to obtain the necessary quality of the end product.
It is also observed that while storing Tenofovir disoproxil in liquid state it is being converted to mono ester of Tenofovir which leads lowering the yield of final product with inferior quality.
It has now been found that base of Tenofovir disoproxil may be obtained as pure and crystalline product, which may be easily handled and conveniently be converted into other pharmaceutically accepted salts.